buprenorphine + ketoconazole

This is a combination of buprenorphine, a partial opioid agonist, and ketoconazole, an azole antifungal and potent CYP3A4 inhibitor. Buprenorphine acts primarily as a partial agonist at the mu-opioid receptor and antagonist at the kappa-opioid receptor, providing analgesic effects with reduced risk of respiratory depression compared to full opioid agonists. Ketoconazole inhibits fungal cell membrane synthesis by blocking lanosterol 14-alpha-demethylase (a cytochrome P450 enzyme) and also strongly inhibits human CYP3A4 enzymes. When co-administered, ketoconazole can increase plasma concentrations of buprenorphine by inhibiting its metabolism via CYP3A4; however, studies show that this interaction is not clinically significant for transdermal or extended-release injectable formulations but may be more pronounced with sublingual forms[1][3][4][5]. This combination does not represent an approved fixed-dose product but rather describes concurrent use.